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Nucleic Acids Res
2020 Jan 08;48D1:D198-D203. doi: 10.1093/nar/gkz1028.
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SEA version 3.0: a comprehensive extension and update of the Super-Enhancer archive.
Chen C
,
Zhou D
,
Gu Y
,
Wang C
,
Zhang M
,
Lin X
,
Xing J
,
Wang H
,
Zhang Y
.
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Super-enhancers (SEs) are critical for the transcriptional regulation of gene expression. We developed the super-enhancer archive version 3.0 (SEA v. 3.0, http://sea.edbc.org) to extend SE research. SEA v. 3.0 provides the most comprehensive archive to date, consisting of 164 545 super-enhancers. Of these, 80 549 are newly identified from 266 cell types/tissues/diseases using an optimized computational strategy, and 52 have been experimentally confirmed with manually curated references. We now support super-enhancers in 11 species including 7 new species (zebrafish, chicken, chimp, rhesus, sheep, Xenopus tropicalis and stickleback). To facilitate super-enhancer functional analysis, we added several new regulatory datasets including 3 361 785 typical enhancers, chromatin interactions, SNPs, transcription factor binding sites and SpCas9 target sites. We also updated or developed new criteria query, genome visualization and analysis tools for the archive. This includes a tool based on Shannon Entropy to evaluate SE cell type specificity, a new genome browser that enables the visualization of SE spatial interactions based on Hi-C data, and an enhanced enrichment analysis interface that provides online enrichment analyses of SE related genes. SEA v. 3.0 provides a comprehensive database of all available SE information across multiple species, and will facilitate super-enhancer research, especially as related to development and disease.
Figure 1. Database content and construction. SEA v. 3.0 takes advantage of available public H3K27ac, BRD4, Med1 and p300 ChIP-Seq datasets to identify super-enhancers in different cell types/tissues/diseases of 11 species. It excludes peaks located within ±2 kb of any RefSeq annotated gene promoter or peaks overlapping with ENCODE blacklisted genomic regions. Multiple track types are used for genomic visualization including functional components generated by Hi-C datasets. Shannon Entropy is used to calculate and evaluate the cell type specificity of super-enhancers, and all data are accessible through the download page.
Figure 2. SEA v. 3.0 update modules. (A) Searching engine updates added three query options. (B) New track types updates include SE constituent computed by Hi-C in multiple cell types and 4D Genome.
Figure 3. A case application showing select SEA v. 3.0 features. (A) Super-enhancers with related coding genes computationally recognized by p300 in chromosome 1 of the human HepG2 cell line. (B) Enrichment analysis of super-enhancer related genes through the Enrichr interface. (C) Cell type specificity of super-enhancers computed by Shannon Entropy. (D) H3K27ac, p300 and Brd4 density of HepG2 super-enhancers visualized in the genome browser. (E) Spatial interaction visualization by Hi-C in the genome region ‘chr1:156864585–156975979’.
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